Vernomigeodiins A–D, highly oxygenated stigmastane-type steroids isolated from Vernoniastrum migeodii with anti-herpes simplex virus activity

Previously undescribed steroids vernomigeodiins A–D (1–4), were isolated from the African medicinal plant Vernoniastrum migeodii along with known sterols 5–10 and the tripeptide aurantiamide acetate (11). The isolated steroids featured a stigmastane skeleton with a unique conjugated Δ^7,9(11)-diene segment and a highly oxidized side chain, occasionally forming a bi- or tricyclic ring system. Sterols 1–3, 5–9 are glucosylated, whereas 4 and 10 are aglycons. The structures of the compounds were elucidated on the basis of 1D and 2D NMR spectroscopy and HRESIMS analyses. The isolated sterols were evaluated for their antiviral activities against Herpes simplex virus type 2. First, their cytotoxicity was assessed in Vero cells using the standard MTT assay, and direct quantitative PCR was then used to evaluate the antiviral activity. Vernomigeodiins A (1) and B (4) and vernonioside B₁ (6) were not cytotoxic up to a concentration of 10 μM but reduced the HSV-2 viral DNA levels with IC₅₀ values between 0.25 and 0.56 μM. In addition, vernoamyoside B (9) showed a direct virucidal effect (IC₅₀ = 1.23 ± 0.15 μM). The interactions between the antiviral compounds and specific viral targets were investigated using molecular docking.